Syndrome of inappropriate antidiuretic hormone secretion

• SIADH (the syndrome of inappropriate antidiuretic hormone secretion) is the commonest cause of hypotonic hyponatraemia in hospital and community practice; the hormone arginine vasopressin (AVP, "antidiuretic hormone") is released when it should be switched off, so the kidney holds on to free water.
• The diagnosis is one of exclusion: low serum osmolality, urine osmolality above 100 mOsm/kg, clinical euvolaemia, urine sodium above 30 mmol/L, and normal kidney, thyroid and adrenal function, with no recent thiazide or other diuretic.
• Severity is judged by symptoms of cerebral oedema (headache and nausea, through vomiting, drowsiness and confusion, to seizures and coma), not by the sodium number alone.
• Fluid restriction below 1 litre a day is first-line in chronic, asymptomatic disease, but it fails in roughly one half of cases; solute (urea 30 to 60 g a day, or up to 9 g of salt tablets), a loop diuretic, or the vasopressin antagonist tolvaptan are the usual next steps.
• Severe symptoms are a medical emergency treated with small boluses of 3% saline to raise the sodium by 4 to 6 mmol/L within one to two hours; correction must then be slowed to avoid osmotic demyelination of the brain.

By the end of this page you should be able to:

1. Explain why SIADH causes dilutional hyponatraemia and yet also sodium loss.
2. List the main causes of SIADH and the common drug causes.
3. Apply the diagnostic criteria and distinguish SIADH from hypovolaemic and hypervolaemic hyponatraemia.
4. Tell SIADH apart from cerebral salt wasting.
5. Recognise the subtypes and "reset osmostat" and say when the diagnosis is not SIADH.
6. Plan emergency treatment of symptomatic hyponatraemia, including safe correction limits.
7. Manage chronic SIADH step by step, including fluid restriction, solute, urea, tolvaptan and its cautions.
8. Describe osmotic demyelination and how to prevent and reverse overcorrection.

The original cases, described in 1957, were two patients with bronchogenic carcinoma who were hyponatraemic yet losing renal sodium; careful water-balance studies showed the cause was continued secretion of the antidiuretic hormone.^[1] It is still common practice to call the condition SIADH; because AVP can be normal or even low in some forms (notably nephrogenic SIADH from a V2 receptor mutation), many authors now prefer the term "syndrome of inappropriate antidiuresis (SIAD)", and this page uses SIADH throughout with SIAD in brackets where helpful.

Plasma sodium is the main determinant of plasma osmolality, and both are held in a narrow range by AVP and by thirst. When serum tonicity rises, hypothalamic osmoreceptor cells release vasopressin; it travels to the renal collecting duct and inserts aquaporin-2 water channels, so water moves out of the filtrate and back into the blood. At the same time thirst is felt. AVP also acts on epithelial sodium channels and on urea transporters to build the medullary osmotic gradient that pulls more water out. The result is concentrated urine and restoration of normal tonicity. Volume receptors (baroreceptors) can override the osmotic system if circulating volume falls, releasing AVP even when tonicity is low: this is appropriate volume defence. In SIADH the baroreceptor and osmoreceptor inputs are overridden by another stimulus, so antidiuresis continues despite low tonicity and despite a normal (or even expanded) circulating volume.

Because SIADH is not a diagnosis of a single disease but a final common pathway, finding the reason for the inappropriate secretion matters: removing the stimulus is the most effective treatment, where possible.

Hyponatraemia of any cause affects between 15% and 30% of acute hospital admissions in most studies; severe hyponatraemia below 125 mmol/L affects about 0.5% to 3%.^[3] In the general population outside hospital the figure is lower (about 1.7% to 7.7%, depending on age and the cut-off used).^[1] Older age is a strong risk factor, largely through accumulated comorbidity and impaired free-water handling, and hyponatraemia is common in residential care.^[1]

SIADH is the single commonest attributed cause of hyponatraemia overall, accounting for roughly 35% to 40% of cases in population-based and prospective studies, and up to about 46% in an unselected hospital population.^[1][3] Severe symptoms are uncommon and are more a function of speed of onset than of the absolute level. Hyponatraemia is mostly mild (plasma sodium at or above 130 mmol/L); only about 4% of hospital patients record a plasma sodium below 130 mmol/L.^{[1] [2]}

The causes of SIADH fall into six groups; any single patient may have more than one stimulus at the same time, and the balance can shift during a hospital admission (pain and nausea, new drugs, administration of hypotonic fluids).^[2]

A prospective single-centre registry of around 1,500 patients with SIADH found the cause was unknown in 35.6%, malignancy in 23.6%, drug-induced in 17.8%, pulmonary disease in 10.7% and CNS disease in 8.5%.^[2] These figures come from association, not proof of causation, and vary between centres (in neurosurgical cohorts CNS disease dominates).^[1]

Drugs can stimulate or potentiate AVP release, activate its receptors, or mimic SIADH by renal salt wasting and other mechanisms.

Vincristine and cyclophosphamide deserve special attention in cancer patients because they pair a tumour stimulus with a tumour treatment and because a post-chemotherapy water load (for example cyclophosphamide with forced diuresis) can produce sudden hyponatraemia; careful fluid management is part of the safety plan. Omeprazole and other proton pump inhibitors are surprisingly common culprits. Desmopressin is not a cause of SIADH in the classical sense but it reproduces the renal effect, and a patient taking it for diabetes insipidus or nocturia should never be fluid-restricted without first stopping the drug.

HIV infection appears in cause lists as well; it is usually associated with CNS or pulmonary disease, or with drug effects, rather than with a direct effect of the virus.^[5]

Some patients have a downward-set osmotic threshold for AVP release; AVP then rises and falls in the right direction but around a lower set point, defending a lower baseline serum sodium. Causes include brain injury, chronic illness, malnutrition, tuberculosis, malignancy, dementia, pregnancy, carbamazepine and venlafaxine. These patients are not water-retaining in the same way: a water load is excreted and the sodium stays stable, and the fractional excretion of uric acid is normal (4 to 11%). The distinction matters, because reset osmostat does not respond to fluid restriction or salt, and it should be identified to avoid unnecessary investigation.^[5]

Nephrogenic SIADH is a very rare X-linked condition from an activating AVPR2 mutation (21 cases reported in 5 family groups). AVP is low but the collecting duct behaves as if it were high. Infants present with cerebral oedema; adult cases can be mild and are diagnosed only after a water load. A low serum copeptin (below about 2.0 pmol/L) with low sodium and osmolality is a clue. The condition affects fewer than 1 per million people.^[1]

In SIADH, water is retained through V2 receptors and aquaporin-2, while volume expansion suppresses aldosterone and raises atrial natriuretic peptide, causing "pressure natriuresis". The net state is increased total body water plus whole-body sodium depletion. The extracellular volume expansion is subtle because most retained water is intracellular; that is why the patient looks euvolaemic.

AVP secretion patterns (Zerbe et al) are useful for understanding, although they rarely change management: persistent elevation (most common, as in malignancy or drugs); "reset osmostat" where the threshold is lowered; and basal elevation with otherwise normal regulation. A fourth pattern, nephrogenic SIADH, has undetectable AVP.

There is also a useful vascular point. Isotonic 0.9% saline has an osmolality of 308 mOsm/L, whereas most patients with significant SIADH run a urine osmolality above 350 mOsm/kg, often 300 to 600 mOsm/kg. Infused saline can therefore be excreted only partly, and the rest of its water is retained: 0.9% saline can worsen the hyponatraemia rather than fix it, and during the infusion it can even overcorrect it. This is why the "normal saline trial" of 1 litre over 12 hours is used as a diagnostic test, and why SIADH is treated with hypertonic saline only when there are severe symptoms. ^[5]

SIADH is essentially a biochemical diagnosis; symptoms come from the hyponatraemia (and from the underlying disease). They depend on level and speed of onset, not on the level alone.

• Mild, asymptomatic hyponatraemia (plasma sodium 130 to 135 mmol/L and slow onset) is often discovered on routine bloods. Even mild chronic hyponatraemia is associated with impaired cognition, attention and gait, more falls, osteoporosis and fractures; these are genuine morbidity, not a laboratory curiosity.^[3]
• Moderate hyponatraemia (125 to 129 mmol/L) typically brings headache, nausea, vomiting, mild confusion, depressed mood, impaired memory and attention, muscle cramps and tremor.^[5]
• Severe or profound hyponatraemia (below 125 mmol/L, or severe/profound by the US definition at or below 120 mmol/L) progresses to vomiting, drowsiness, confusion, abnormal somnolence, seizure, coma and, rarely, respiratory arrest and death from cerebral oedema and herniation. Acute symptomatic hyponatraemia has a high mortality if untreated.^[3]
• Chronic hyponatraemia (more than 48 hours) adapts: astrocytes lose intracellular solutes and organic osmolytes, so brain volume stays near normal and symptoms are milder. The downside is vulnerability to rapid correction, because the lost osmolytes recover slowly.

On examination the patient is clinically euvolaemic: no tachycardia, postural hypotension, dry mucous membranes, peripheral oedema, raised jugular venous pressure or ascites. The absence of hypovolaemic signs (hypokalaemia, hyperkalaemia or acid-base disturbance) is itself a pointer, because these are not features of SIADH.^[2] An underlying cause is often found by looking again: small cell lung cancer presents with cough, haemoptysis and weight loss; pituitary surgery gives a classic 5- to 12-day sodium nadir; a postoperative patient has pain, nausea and fluid administration.

Although subtyping by AVP response to osmotic stimulus is rarely done in practice, two are worth knowing. Type A SIADH shows persistently raised AVP regardless of osmolality (malignancy, most drugs). Reset osmostat is the altered-threshold form above. Accurate duration categories use the European cut-offs: mild 130 to 135 mmol/L, moderate 125 to 129, profound below 125; acute and chronic are separated at 48 hours. ^[3]

The differential is the diagnosis of hypotonic hyponatraemia, and volume status is the organising question.

Cerebral salt wasting (CSW) occurs with intracranial disease (classically subarachnoid haemorrhage). It is a true volume-depleted, natriuretic state, probably driven by B-type natriuretic peptide from the injured brain, not by AVP. It mimics SIADH in every urine value, so the distinction is clinical.

CSW accounts for under 10% of hyponatraemia in subarachnoid haemorrhage, so SIADH is still the likelier diagnosis, but missing CSW matters because fluid restriction in a volume-depleted patient can promote cerebral vasospasm. Both conditions respond to hypertonic saline while the diagnosis is being sorted, which is fortunate. CSW is usually transient, resolving within three to four weeks, and once the patient can take medication it can be managed with salt tablets or fludrocortisone.^[3][5]

• Hypovolaemic hyponatraemia (vomiting, diarrhoea, burns, pancreatitis, diuretics) responds to 0.9% saline and shows low urine sodium below 30 mmol/L without diuretics; SIADH and diuretic use give urine sodium above 30.
• Thiazide-induced hyponatraemia can be euvolaemic and biochemically identical; urine sodium and osmolality look like SIADH, so a careful drug history is the clue, and recovery after stopping the drug confirms it.
• Primary adrenal insufficiency gives hypovolaemic hyponatraemia; secondary adrenal insufficiency is euvolaemic and indistinguishable from SIADH, so morning cortisol is mandatory in every case. Glucocorticoid replacement fixes it.
• Severe hypothyroidism rarely causes hyponatraemia and only at very low levels; thyroid function tests should be requested but not over-interpreted in sick patients.
• Hypervolaemic hyponatraemia (heart failure, cirrhosis, nephrotic syndrome) is clinically obvious from oedema and raised jugular venous pressure.
• Primary polydipsia and "beer potomania" / low-solute intake produce dilute urine with osmolality below 100 mOsm/kg; polydipsia also gives high urine volume above 3 litres a day.
• Advanced renal failure (GFR below 15 ml/min) impairs free water excretion and produces urine osmolality around 200 to 250 mOsm/kg despite suppressed AVP. ^[5]
• Exercise-associated hyponatraemia and acute postoperative dilutional hyponatraemia (including transurethral resection syndrome) are acute, often with minimal urine dilution, and can be fatal. They are covered as medical emergencies rather than as SIADH.

Cross-check with the hyponatraemia topic in Renal for the volume-based algorithm: this page focuses on the SIADH limb, while the Renal page walks the whole hypotonic hyponatraemia algorithm.

Blood and urine tests (ideally before intravenous fluids):

• Serum sodium, potassium, urea, creatinine, glucose, osmolality (serum osmolality under 275 mOsm/kg confirms hypotonic hyponatraemia; correct for glucose before calling it hypotonic).
• Urine osmolality and sodium (and potassium, so the sodium-to-potassium ratio for the Furst formula can be calculated).
• Morning cortisol and thyroid function tests to exclude adrenal and thyroid disease.
• Uric acid (low, under 4 mg/dL, and fractional excretion above 12% support SIADH). ^[2]
• Blood gas sodium if pseudohyponatraemia is suspected; direct ion-selective electrodes are immune to the lipid and protein interference.

Imaging and further work-up depends on cause and recurrence: chest CT, brain imaging, sinus imaging, and occasionally DOTATATE PET to look for an occult AVP-producing neuroendocrine tumour. In frail older patients an extensive search may not be warranted beyond morning cortisol, because SIADH is often idiopathic.^[2] If a patient has chronic or recurrent hyponatraemia with no clear cause, CT of chest, head and sinuses is appropriate.^[4]

The diagnostic criteria (Bartter and Schwartz, 1967) have changed little. Euvolaemia is a prerequisite and must be established from the history and examination (no recent diarrhoea or vomiting, no diuretic use; no peripheral oedema, ascites, raised jugular venous pressure). All six main criteria must be met.

Each criterion needs a brief comment. Plasma osmolality under 275 mOsm/kg must be confirmed (not just low sodium), and hypertonic hyponatraemia from glucose or mannitol must be excluded first. Urine osmolality above 100 mOsm/kg means free water cannot be cleared (most SIADH patients run 300 to 600 mOsm/kg). The urine sodium threshold is 30 mmol/L in European and US guidance, although several sources use above 40 mmol/L. Renal function must be reasonable (GFR under 15 mL per minute impairs free-water excretion on its own). Thiazides especially must be excluded. Adrenal insufficiency is a common mimic, so morning cortisol is not optional. ^[2]

Management is driven by three questions in order: (1) are there moderate to severe symptoms of cerebral oedema, (2) is it acute (under 48 hours) or chronic (over 48 hours or unknown), and (3) what is the volume status and cause. A fourth is whether the brain is at high risk of ODS (plasma sodium at or below 105 mmol/L, alcohol use, malnutrition, hypokalaemia, hypophosphataemia, advanced liver disease).

Severe symptoms (vomiting, confusion, seizures, coma) are a medical emergency. Hypertonic saline is the treatment, ideally in a monitored setting; bolus therapy achieves a faster initial rise and better neurological recovery than continuous infusion. ^[3]

The practical UK consensus suggests 150 mL of 3% saline over 15 minutes, repeated once if no clinical improvement, with the aim of a 4 to 6 mmol/L rise in the first 6 hours and a ceiling of 10 mmol/L in 24 hours. ^[4] Only small boluses are used, with frequent sodium checks (every 1 to 2 hours until above 120 mmol/L). Hypertonic saline should normally be stopped once severe symptoms resolve or sodium has risen by 5 mmol/L, and the total 3% saline dose should be reconsidered after 300 mL. ^[5] One useful rule: if you reach 300 mL of 3% saline, reassess before giving more. ^[5]

ODS risk is shaped by the level and by the patient. Almost all reported ODS is in patients admitted with plasma sodium below 120 mmol/L (many at or below 105 mmol/L), and risk is far higher in alcohol misuse, malnutrition, severe liver disease, hypokalaemia, hypophosphataemia and older adults. ^{[1] [2]} Guidelines differ in their exact numbers; what is not in dispute is that limits are limits, not targets.

An additional, easily forgotten rule: when a large water diuresis is expected after the cause resolves (postoperative state, after nausea settles), desmopressin (1 to 2 micrograms intravenously or subcutaneously every 6 to 8 hours) is a standard way to prevent aquaresis and stop the sodium running away. Urine output must be monitored alongside serum sodium.

The primary treatment of SIADH is to remove the stimulus: stop an SSRI, treat pneumonia, correct hypoxia, relieve pain and nausea in the postoperative patient, stop desmopressin, and in malignancy treat the cancer where possible. Where the cause is not identifiable and not treatable, the anti-antidiuresis strategies below are used.

Fluid restriction is recommended as first-line in both European and US guidance for chronic, asymptomatic SIADH. The aim is a negative electrolyte-free water balance. A restriction below 1000 mL a day is the standard starting point; many patients need 500 to 800 mL a day. ^[1]

Response can be predicted with the Furst (urine-to-plasma electrolyte) ratio:

U/P electrolyte ratio = (urine sodium + urine potassium) / serum sodium (all in mmol/L).

• U/P below 0.5: restrict to 1000 mL a day.
• U/P 0.5 to 1.0: restrict to 500 mL a day.
• U/P above 1.0: virtually no free-water clearance occurs; fluid restriction is unlikely to help. ^[4]

Fluid restriction works in only around half of cases (39% to 55% fail). ^{[1] [2]} A randomised trial of 1 litre a day versus no restriction in 46 patients found the plasma sodium rose by 3 mmol/L at day 3 and by 4 mmol/L at day 30 in the restriction arm, against 1 mmol/L at both points in controls. ^[1] A high urine osmolality (above 500 mOsm/kg) and a high urine sodium (above 130 mmol/L) predict non-response better than the Furst ratio itself. ^[1] Where restriction is unlikely to work, move promptly to solute or a vaptan rather than delay for weeks.

Mechanical tips worth using: fluid balance charts, bedside notices, removal of excess bedside water, and telling staff with tea rounds and volunteers not to offer drinks. Daily electrolytes and clinical review are mandatory.

If restriction fails (or is not acceptable), the next step is to increase urinary solute excretion, so that more free water leaves with it. These are the European guideline second-line options and are cheap and well tolerated.

• Urea: 30 to 60 g a day, in divided doses and usually in divided sachets, mixed with sweetener or orange juice for taste. A single 15 g sachet provides 250 mOsm of renal solute load, compared with 34 mOsm from a 1 g salt tablet, so urea is several-fold more effective. A systematic review of 26 studies in 462 patients reported a median plasma sodium rise of 4.9 mmol/L over 24 hours and 9.6 mmol/L over 5 days, with mainly dysgeusia and no cases of ODS (urea may even be protective against ODS in animal models). Urea can be used long term. ^{[1] [2] [5]}
• Salt tablets: 9 g a day (3 g three times a day) provides the sodium of 1 litre of 0.9% saline, absorbed gradually, so rapid sodium swings are uncommon. They suit younger SIADH patients with no comorbidity; use cautiously in hypertension and left ventricular dysfunction. ^[5] Sodium chloride alone, without a diuretic, often has insufficient solute load (6 g gives only about 198 mOsm a day; compare 500 mOsm from 30 g of urea). ^[1]
• High-protein diet: one gram of protein generates about 5.6 mmol of urea; trials show a high-protein diet can raise plasma sodium in SIADH, at low cost. ^[2]
• Loop diuretics (furosemide 20 mg twice daily or torsemide 20 mg daily) with close electrolyte monitoring lower urine osmolality to roughly half of its previous value (for example from 500 to 250 mOsm/kg) and enhance the effect of salt or urea. Renal dysfunction is common with prolonged use in euvolaemic patients, potassium losses need replacing, and the combination with saline risks rapid correction. Give cautiously. ^{[2] [5]}

A note on 0.9% saline in SIADH: it acts as a hypertonic solution during infusion and can both overcorrect sodium and then worsen it after the infusion stops, because the kidney excretes the sodium but retains much of the water. Avoid it in moderate-to-severe SIADH. It is appropriate for a mild hyponatraemia of unclear cause as a diagnostic challenge (500 mL to 1 litre, then recheck sodium), and for hypovolaemic hyponatraemia. ^[5]

Tolvaptan is an oral, V2-selective receptor antagonist that attacks the mechanism directly, producing aquaresis without sodium loss. It is the only drug class approved (in the United States) for hyponatraemia.

• Dose: start with a single dose of 15 mg orally once daily, with monitoring of serum sodium 6 hours after the first dose. Drug experience is limited and use should be restricted to specialists experienced with it; prescription as a single dose, not a repeat, with no more than two or three doses needed in many cases. Remove fluid restriction first and let the patient drink to thirst, because combined restriction and tolvaptan can overcorrect rapidly. ^[4]
• Effectiveness: the SALT-1 and SALT-2 trials (448 hyponatraemic patients, 42% with SIADH) showed faster normalisation of plasma sodium with tolvaptan than with placebo over 30 days, with improved quality-of-life scores, and a SALTWATER extension followed 111 patients for a median of 1.9 years. ^[2]
• Overcorrection: 28.6% of SIADH patients given 15 mg of tolvaptan corrected plasma sodium by more than 12 mmol/L per day, and 39.3% by more than 8 mmol/L per day. A lower starting dose of 7.5 mg (3.75 mg in high-risk patients) probably reduces this risk; randomised trials are still needed. ^[2] Concomitant tolvaptan and loop diuretics is a particular hazard.
• Liver caution: the FDA advises against tolvaptan in liver disease and limits use to 30 days. The concern came from the TEMPO 3:4 trial in autosomal dominant polycystic kidney disease, which used far higher doses and far longer than are used for hyponatraemia. Tolvaptan is not the same as a hepatotoxin in standard SIADH regimens, but the interdiction stands. ^[2]
• Cost: high (around 300 US dollars per tablet in older US data) and vaptans are not routine in many systems.
• Other vaptans: conivaptan (intravenous, V1 and V2 antagonist) is limited to 4 days because of CYP3A4 inhibition. ^[2]
• Overcorrection on vaptans can be hard to reverse: because V2 receptors are blocked, desmopressin may not work and 5% dextrose is used instead. If the limit has been exceeded, desmopressin plus dextrose 5% is the standard rescue. ^[2]

The European 2014 guideline (ESE/ESICM/ERA/EDTA) and the US expert panel (Verbalis 2013) agree on fluid restriction first and hypertonic saline for emergencies, but they split on second-line therapy.

• Europe: after restriction fails, recommend urea or sodium chloride with a loop diuretic, and treat vaptans as third line; mildly recommends against vaptans in mild-to-moderate SIADH and recommends against them in profound SIADH unless restriction and solute fail.
• US: recommend fluid restriction, then vaptan therapy; reserve solute and diuretic to later or not at all.

A practical reading: use cheap, reversible solute (urea first) in a stable patient, and reserve tolvaptan for inpatient use where rapid correction is clinically needed and the dosing and monitoring can be done properly. Tolvaptan should not be combined with restriction.

Demeclocycline (an indirect antagonist that induces reversible nephrogenic diabetes insipidus) is effective in about 60% of SIADH but is unpredictable, slow (days), hepatotoxic and nephrotoxic, expensive and is specifically recommended against by the European guidelines. It remains licensed in the UK for malignant SIADH where restriction has failed and there is no liver cirrhosis, at 150 mg three times daily and up-titrated after 3 days. ^{[4] [2] [5]} Urea is generally the better drug now.

SGLT2 inhibitors (empagliflozin) improve serum sodium by glucosuric osmotic diuresis; two small trials are positive and the drug is well tolerated. A US pilot suggested modest benefit in SIADH. Evidence is still limited and the use is off-label and usually third line. ^{[1] [2]}

This is the key dangerous complication of treatment, not of the disease itself, and it is preventable.

When hyponatraemia develops gradually, the brain adapts by losing intracellular solutes, including glutamate and other organic osmolytes. If plasma tonicity then rises too fast, astrocytes shrink faster than they can reclaim those solutes and undergo apoptosis; the result is demyelination of pontine and extra-pontine neurones. Symptoms appear 1 to 6 days later: dysarthria, dysphagia, brisk jaw jerk, pseudobulbar palsy, catatonia, dystonia, tremor, myoclonus, limb paralysis (including the locked-in state), seizures, coma and death. The locked-in patient can be awake but unable to move or communicate. Partial or complete recovery is common, even in the worst cases, and supportive care should be continued for weeks before any withdrawal-of-care decision. ODS does not occur with rapid correction of acute hyponatraemia, because adaptation has not yet occurred. ^{[3] [2] [5]}

Risk profile: plasma sodium at or below 105 mmol/L in almost all cases (and rarely above 120); risk factors of alcohol misuse, malnutrition, severe liver disease, hypokalaemia, hypophosphataemia. Case reports exist after correction of less than 12 mmol/L in high-risk patients. ^{[1] [2]}

The prevention rules (European 2014): no more than 10 mmol/L rise in plasma sodium in the first 24 hours and 8 mmol/L per 24 hours thereafter (18 mmol/L in 48 hours). US guidance: 4 to 8 mmol/L for chronic disease, with a ceiling of 8 to 12 mmol/L per day and a stricter ceiling of 4 to 8 mmol/L per day in patients at high risk. Most guidance also holds to 4 to 6 as a safer first target in the first few hours even after severe symptoms. If overcorrection has occurred, dextrose 5% with or without desmopressin should be used to re-lower the plasma sodium to just below the limit. ^{[2] [4]}

Mortality in SIADH is driven by the underlying disease (small cell lung cancer, for example), not by the sodium; deaths attributed to treatment errors (overcorrection and ODS, or undertreatment of cerebral oedema) are the avoidable ones. Hyponatraemia is associated with both higher inpatient and post-discharge mortality, but whether treatment of the sodium itself improves survival has not been proven. Chronic, treated, mild-to-moderate hyponatraemia still carries meaningful morbidity: cognitive and attention deficits, gait instability, falls, osteoporosis, fractures, prolonged length of stay. Correction of the sodium is associated with improvement in neurocognitive scores. ^[3] Severe hyponatraemia is rare and treatable, so the prognosis in SIADH is usually that of the underlying cause.

• Pregnancy: SIADH is uncommon but can occur with oxytocin infusion, or with conditions that cause similar physiology; management uses the same principles but with specialist obstetric input. Desmopressin is used if diabetes insipidus coexists.
• Children: SIADH is rare; the commoner paediatric issue is postoperative or drug related. Correction limits are proportionally stricter.
• Older adults: high risk; the idiopathic form is common. An extensive tumour search beyond morning cortisol is often not warranted, but malignancy must be considered if presentation is new or recurrent. Falls and cognitive effects of chronic hyponatraemia matter.
• Postoperative patients: pituitary and non-pituitary surgery produce a classic triphasic sodium curve, peaking 6 to 12 days after surgery. Prophylactic fluid restriction (1000 mL a day from day 4 to 9, with a sodium check at day 7) is recommended if AVP deficiency does not occur. Management otherwise follows chronic SIADH. The episode is usually self-limiting, resolving within about 5 days. ^[1]
• ICU settings with intracranial pathology: 23.4% hypertonic saline (30 mL as an intravenous push over 10 minutes through a central line) has been used for raised intracranial pressure in traumatic brain injury; SIADH still accounts for most hyponatraemia even in this population and resolves faster than expected once the neurological condition stabilises.

Where 3% saline, urea formulation, vaptans, cortisol assays and imaging are not available, the following remain practical and evidence based.

• Check the basic chemistry (sodium, potassium, urea, creatinine, glucose and simple osmolality if possible), and do not skip the morning cortisol and TSH in any euvolaemic patient; these two tests change management the most and are cheap.
• Diagnose SIADH clinically: euvolaemia plus urine that is inappropriately concentrated (any measurable osmolality unit above 100) and a urine sodium that does not suggest depletion. A side-room urine specific gravity above 1.005 in this context supports it.
• Fluid restrict to half a litre to a litre daily (thirst permitting) as first line; document it with a balance chart. Patient and family education is part of the treatment, because visitors bring water.
• If restriction fails or is not feasible, increase solute intake cheaply: food protein (eggs, beans, meat, dairy) rather than expensive urea sachets; table salt dissolved in water at low cost; furosemide 40 mg once daily with potassium chloride replacement and renal monitoring.
• Avoid 0.9% saline in established SIADH; it commonly does not help and can overcorrect or worsen the balance.
• Ensure hypertonic saline is available for emergencies as 3% (or locally available hyperosmolar solutions) in small boluses only; a single 100 mL bolus repeated once or twice is the correct start, with sodium checked as soon as possible and strict ceiling control thereafter.
• Prevent overcorrection with the simplest measures: small saline volumes, frequent (every 1 to 2 hours at first) sodium checks, and the cheapest rescue, oral or intravenous water plus desmopressin if it is available. If desmopressin is unavailable, close observation and strict fluid restriction after a rapid rise is the fallback, with earliest possible referral.
• Send every patient with recurrent, severe or young-onset SIADH to a centre that can image (chest and brain) and measure cortisol properly; many causes are treatable curable (pneumonia, offending drug) once found.

• Hyponatraemia (renal): the whole hypotonic hyponatraemia algorithm, volume assessment, and hypertonic saline tables.
• Hypernatraemia: the mirror problem, and how osmoregulation fails at high sodiums.
• Diabetes insipidus: the V2/AQP2 axis failing in the opposite direction (and where desmopressin is treatment, not cause).
• Thiazide diuretics: a common mimic of SIADH and a cause of severe hyponatraemia even with normal renal function.
• SIADH-producing malignancies: small cell lung cancer (cause lists above).
• Secondary adrenal insufficiency / hypopituitarism: the SIADH mimic that changes management completely.
• Acute kidney injury and chronic kidney disease: impaired free-water excretion when GFR falls below 15 mL per minute.
• Low-resource settings: the last section above.